ABSTRACT
Objective:To analyze the clinical phenotypes and pathogenic gene of a Han Chinese family with enhanced S-cone syndrome (ESCS).Methods:The method of pedigree investigation was adopted.A suspected ESCS Han Chinese family including 8 members of 3 generations was recruited in Henan Eye Hospital from June to September 2021.There was one patient in the family.A thorough ophthalmic examination of the proband was carried out to evaluate the phenotypes, including visual acuity, degree of strabismus, anterior segment and fundus, autofluorescence imaging, fluorescein fundus angiography, full-field electroretinogram (ERG), multifocal ERG, optical coherence tomography.DNA was extracted from peripheral blood samples from the proband and family members.The pathogenic gene and variation were screened by whole exome sequencing (WES).The variation and co-segregation were verified by Sanger sequencing.The deleteriousness of the variation was analyzed by SIFT, Polyphen2 and MutationTaster.The pathogenicity of the variation was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines.The analysis of amino acid sequence conservation was performed by SIFT.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2017[6]).Written informed consent was obtained from each subject.Results:This pedigree was consistent with autosomal recessive inheritance.The proband had clinical features such as night blindness, hyperopia, accommodative esotropia, peripheral retinal pigmentation, retinoschisis, and photopic ERG responses dominated by large-amplitude waves.Variations including a compound heterozygous variation, c.671C>T: p.S224L on exon 5 and c. 955G>A: p.E319K on exon 6 of NR2E3 were identified by WES.The variations were confirmed to be consistent with co-segregation.The both loci were missense variations, the variation frequency of which was 0 in the East Asian population via the gnomAD database.The variations were predicted to be deleterious by SIFT, Polyphen2 and MutationTaster.The c.671C>T variation was recorded with unknown significance in ClinVar database, and the c.955G>A variation was an unreported new locus.According to the ACMG Standards and Guidelines, the both variations were labeled as with uncertain clinical significance, and the corresponding amino acid sequences were highly conservative across multiple species. Conclusions:This family has the clinical characteristics of ESCS and meets the genetic diagnosis criteria.Two novel variations in NR2E3 gene, c.671C>T: p.S224L and 955G>A: p.E319K, are found.
ABSTRACT
Objective To identify the pathogenic genes and mutations in a Hui population family with Goldmann-Favre syndrome.Methods A two-generation Hui population family with consanguineous marriage including 4 individuals was enrolled in this study.DNA was extracted from 4 ml peripheral venous blood of all participants.The DNA sequence was performed by Ophthalmology Gene panel sequencing through Ion PGM platform.Then the selected mutations were proved by PCR-Sanger sequencing method.Pathogenic analysis of the mutation was done by means of retrieving PubMed and related databases.And the function of mutation effect was interpreted by protein prediction software.Results The sequence result showed that a novel homozygous mutation in NR2E3,c.925C ＞ T (p.R309W),which resulted in conversion of arginine to tryptophan at position 309 of the photoreceptor-specific retinal nuclear receptor.Parents of the proband were carriers of the heterozygous mutation.The 309 amino acid locus of NR2E3 protein product was highly conserved among species,and protein prediction softwares predicted the mutation as harmful.Conclusion The homozygous mutation c.925C＞T (p.R309W) in NR2E3 cause Goldmann-Favre syndrome in this patient.